The effect of a cognitive training therapy based on stimulation of brain oscillations in patients with mild cognitive impairment in a Chilean sample: study protocol for a phase IIb, 2 × 3 mixed factorial, double-blind randomised controlled trial

Background The ageing population has increased the prevalence of disabling and high-cost diseases, such as dementia and mild cognitive impairment (MCI). The latter can be considered a prodromal phase of some dementias and a critical stage for interventions to postpone the impairment of functionality. Working memory (WM) is a pivotal cognitive function, representing the fundamental element of executive functions. This project proposes an intervention protocol to enhance WM in these users, combining cognitive training with transcranial electrical stimulation of alternating current (tACS). This technique has been suggested to enhance the neuronal plasticity needed for cognitive processes involving oscillatory patterns. WM stands to benefit significantly from this approach, given its well-defined electrophysiological oscillations. Therefore, tACS could potentially boost WM in patients with neurodegenerative diseases. Methods This study is a phase IIb randomised, double-blind clinical trial with a 3-month follow-up period. The study participants will be 62 participants diagnosed with MCI, aged over 60, from Valparaíso, Chile. Participants will receive an intervention combining twelve cognitive training sessions with tACS. Participants will receive either tACS or placebo stimulation in eight out of twelve training sessions. Sessions will occur twice weekly over 6 weeks. The primary outcomes will be electroencephalographic measurements through the prefrontal theta oscillatory activity, while the secondary effects will be cognitive assessments of WM. The participants will be evaluated before, immediately after, and 3 months after the end of the intervention. Discussion The outcomes of this trial will add empirical evidence about the benefits and feasibility of an intervention that combines cognitive training with non-invasive brain stimulation. The objective is to contribute tools for optimal cognitive treatment in patients with MCI. To enhance WM capacity, postpone the impairment of functionality, and obtain a better quality of life. Trial registration ClinicalTrials.gov NCT05291208. Registered on 28 February 2022. ISRCTN87597719 retrospectively registered on 15 September 2023. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-024-07972-7.


Research Objectives:
The aim of this research is to evaluate the effect of a combined intervention involving cognitive training and brain electrical stimulation in a group of individuals with Mild Cognitive Impairment compared to an intervention involving only cognitive training.
Brain electrical stimulation is a widely used clinical technique that safely and non-invasively allows the stimulation of certain regions of the brain by applying low-intensity electric current to the patients' scalp.The most commonly reported adverse effect is a mild discomfort (irritation or itching) in the application area of the current, and if the discomfort persists, the session will be immediately suspended.The type of current you may receive can be real (providing actual electric current) or placebo (simulating the perceived sensation but not actually applying electric current).
On the other hand, cognitive training will involve the completion of tasks in front of a computer in a room equipped for three people, accompanied by a monitor who will guide and resolve any queries.These tasks have been specially designed to train the cognitive ability of working memory (the capacity that allows us to maintain and temporally manipulate information to guide our behavior towards a specific goal).
All procedures will take place at the Center for Speech and Hearing Care of the University of Valparaíso (CAFUV).

PROCEDURE DETAILS:
Participation in this project involves four stages, which are detailed in the following outline:

Project Stages
Group 1 Group 2 Pre-treatment Assessment RISKS: All procedures in this research involve no risks for the participants.The most common adverse reaction is a mild discomfort (irritation or itching) in the area of application of the electrical brain stimulation.If the discomfort persists, the session will be immediately suspended.

COSTS AND COMPENSATION:
All evaluations and procedures included in the study will be free of charge.Participants will be compensated for transportation expenses at the end of each session.
Although no risks associated with the applied procedures have been described, in the event of any adverse event directly related to the application of this protocol, the participant will be referred to a consultation with the neurologist associated with the project.This appointment will not incur any costs for the participant, and any doubts will be resolved, and guidance will be provided for the continuity of treatment at the appropriate health facility, if necessary.These costs will not be covered by the funds of this project.

DATA RETURN:
At the end of the study, a descriptive and non-diagnostic report will be delivered to the participant in person.

CONFIDENTIALITY:
Although the results obtained are intended to be published in scientific journals, the identity of each participant will be kept confidential and coded.Any person not involved in this research lacks access to information that would identify the volunteers participating in this study.The data obtained will be stored digitally, in duplicate, on different media (hard disk and DVD as a backup) for the duration of the study at the Center for Social Complexity Research of the Universidad del Desarrollo.Once the study is completed, the data will be stored only on solid media (DVD) on the university premises, to have a backup for the eventual verification of results and analysis procedures.
It is possible that the data collected in the context of this research may be used in subsequent studies that benefit from the type of records obtained.If this is the case, only coded data will be available, maintaining the identity of each participant strictly confidential.

PARTICIPATION IN THE STUDY:
The decision to participate in this study is entirely voluntary and personal.Granting consent as a participant will have no impact on the regular treatment you receive.
Similarly, if you were to feel uncomfortable and wish to withdraw from the study, you are free to do so at any time and without any consequences.

SAMPLE SELECTION:
The selection of participants will be conducted by the clinical team at the Center for Speech Therapy Care at the University of Valparaíso (CAFUV), based on users with Mild Cognitive Impairment referred to the center.

COMMUNICATION WITH THE PRINCIPAL INVESTIGATOR:
If If you agree to participate in this study, you must sign two copies of this Informed Consent.One copy will be for the investigator who explained each of the points of the research, and the other copy is for you to keep once signed.

DECLARATION OF THE PARTICIPANT
In the present study, _____________________________________________ (name of the informing researcher) has clearly explained to me, both verbally and in writing, that I will be participating in the research project titled "Evaluation of a cognitive training therapy based on brain oscillation stimulation in patients with Mild Cognitive Impairment through a randomized clinical trial" with the identification code FONIS Folio SA19I0118.I understand that my participation will include a cognitive assessment of performance in working memory tasks, an electroencephalographic recording, and a cognitive intervention program along with electrical brain stimulation, either real or placebo.Furthermore, I am aware that each phase of the study will have a maximum duration of 60 minutes.
Considering all of the above, I _____________________________________________ voluntarily confirm my participation in this research.Likewise, I affirm that I have had the opportunity to clarify all my doubts, and that Dr. Pablo Billeke Bobadilla has expressed his availability to assist me should any additional questions arise.Also, I acknowledge that if I feel uncomfortable and wish to withdraw from the study, I am free to do so at any time and without any consequences.Date and time: ___________________________________________________________________

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As a participant in this research, you will not receive a direct benefit.Instead, you will contribute to a better long-term understanding of this condition and new treatment alternatives. you have any doubts or questions about this research, you can contact the responsible investigator: Pablo Billeke Bobadilla Laboratory of Social Neuroscience and Neuromodulation Center for Research in Social Complexity Faculty of Government, Universidad del Desarrollo, Chile Av.Las Condes #12461, Tower 3, Office 307, Las Condes, Santiago Tel.02-232 79 636.pbilleke@udd.clApproval: This study has been approved by the Scientific Ethics Committee of the Universidad del Desarrollo.In case of any inquiries about your rights as a participant in the study or in the event of any potential conflicts, you can contact Dr. Marcial Osorio, President of the Scientific Ethics Committee of the Universidad del Desarrollo (Faculty of Medicine UDD / Clínica Alemana de Santiago, Avenida Las Condes #12461, Tower 3, 2nd floor, Las Condes, Santiago de Chile.Phone (562) 3279157, e-mail: ceccasudd@udd.cl).